PsycENCODE: Exploring the Function of Non-coding Elements in the Brain

Presenter

Goal

This initiative aims to support studies on mental disorders based on new concepts of transcriptome complexity that assign functional roles to non-coding and potentially novel coding transcripts, exploring their potential as trans-regulators of gene transcription, mRNA splicing, mRNA stability, molecular transport, and influence on chromosome architecture.

Rationale

The completion of the human genome sequence was a watershed event in understanding human biology and has led to a plethora of new insights into the complexity and structure of the genome. One of the most striking findings was the relatively small number of protein coding sequences relative to the size of the genome and the resulting obvious question: what is the rest of the genome for? Results from the ENCODE and modENCODE projects and the brain transcriptional atlas indicate that significant portions of the genome, beyond the known RefSeq coding sequences, are highly conserved, and much of the conserved sequence gives rise to transcripts of unknown function (TUFs). These TUFs include non-polyadenylated and non-ribosomal RNAs as well as polyadenylated transcripts with potential regulatory roles. They arise from intergenic and intragenic (introns and 3’/5’ nontranlated) regions as well as psuedogenes and potential coding sequences from unannotated genes. TUFs include such designations as hetero-nuclear RNA, micro-RNA, and small nuclear-RNA. Our understanding of how these transcripts impact function, potentially contributing to disease phenotypes, is at an early stage. However, some TUFs exhibit developmental and spatial specificity in their expression profiles suggesting functional roles in tissue phenotype.